Glutamine synthetase (GS) is a strategic target for hormonal regulation of nitrogen metabolism because the amide nitrogen of glutamine is utilized for the synthesis of a wide variety of compounds. We find that glutamine synthetase specific activity increases more than 100-fold during the insulin-mediated adipocyte conversion of 3T3-Ll cells, that incubation of 3T3-Ll adipocytes for 3 days with dibutyryl cyclic AMP plus theophylline results in more than a 90% decrease in glutamine synthetase specific activity and that hydrocortisone increases GS activity in both 3T3-Ll adipocytes and in 3T3-ll preadipocytes. We find by immunotitration of GS activity that the marked changes in 3T3-Ll adipocyte GS are due to changes in the cellular concentration of GS molecules and not due to changes in the activity of each molecule. Our current effort is directed at determining by radioimmunochemical methods the effects of hormones and effectors on the rate of GS synthesis and degradation in 3T3-Ll adipocytes. In addition we will determine whether GS in 3T3-Ll adipocytes might be subject to regulation by covalent modification.